A study led by scientists at Rutgers University-New Brunswick has shown that specialized cells involved in how the body responds to insulin are activated in the brain after exercise, suggesting that physical activity may directly improve brain function.

A study, published in Aging Cell, a journal focused on the biology of aging, indicates that therapies targeting this insulin action may be developed to offset or even prevent dementia progression.

We believe this work is important because it suggests exercise may work to improve cognition and memory by improving the abilities of insulin to act on the brain.”

Steven Malin, associate professor in the Department of Kinesiology and Health in the Rutgers School of Arts and Sciences and lead author of the study

Conducted in collaboration with the National Institutes of Health’s National Institute on Aging, the researchers focused on the role of neuronal extracellular vesicles, specialized cells released by the brain.

Extracellular vesicles, once dismissed by researchers as “cell dust,” have in the past 15 years grown exponentially in recognition as important players in the microscopic world of the human body, facilitating transport of key molecules such as proteins between cells. For this study, the scientists targeted vesicles produced in the brain that ferry several proteins involved in insulin sensitivity – one of which is called Akt.

Insulin sensitivity is a measure of how well the body responds to insulin, a hormone that controls blood sugar levels. People with high insulin sensitivity can use blood glucose more effectively in the body, such as in its muscles, which reduces blood sugar. People with diabetes, with its key symptom of low insulin sensitivity or insulin resistance, have brain cells that are less responsive to insulin. This can have negative impacts on cognition.

Researchers were able to study the vesicles by isolating them in the blood of participants in an experimental study. The trial, conducted over two weeks, included a group of 21 volunteers who had an average age of 60 and had prediabetes. Over the course of the study, they engaged in 12 individual, supervised, 60-minute exercise sessions of moderate to high intensity. The participants ingested a glucose drink before and after training. Researchers then collected blood samples before and during the drink from the participants at the start and end of exercise training.

The blood samples showed that the number of neuronal vesicles carrying proteins involved in insulin sensitivity increased after each training, with Akt being most notable.

“We showed for the first time that exercise impacts insulin signaling from neuronal extracellular vesicles in relation to clinical improvements in blood sugar,” Malin said. “And we use these neuronal extracellular vesicles as an indicator of brain insulin sensitivity.” 

Exercise, therefore, is potentially able to improve the brain’s capacity to respond to insulin for neuronal function, he said.

Insulin is a hormone increasingly recognized to regulate cognition, the mental process of acquiring knowledge through thought, experience and the senses. Prediabetes is a serious health condition that occurs when blood sugar levels are higher than normal but not high enough to be diagnosed as Type 2 diabetes. Those with prediabetes run the risk of having insufficient levels of insulin in their bodies, particularly the brain, which increases the chances of developing diseases of dementia such as Alzheimer’s, Malin said. 

Insulin also plays a crucial role in memory formation, recall, processing speed and the functioning of synapses, structures that allow brain cells to communicate with one another. 

“If insulin is insufficient in the brain, that means not only will brain cells become potentially dysfunctional, but also they may fail to interact with each other properly,” Malin said. “It’s like playing the game telephone with a friend. At some point the message gets lost when the brain becomes insulin resistant.”

Exercise has long been believed to improve cognition, but the mechanisms involved have been unclear. Past studies have uncovered evidence that high blood sugar contributes to a decrease in the brain’s ability to recall information and learn new information.

Malin said that insulin, which is produced by the pancreas and travels to the brain to perform its functions, plays a central role in promoting brain blood flow and neuronal functioning for cognition.

“Our work suggests that therapies that target brain insulin action may be able to ward off dementia,” Malin said.

In a new study, Malin and his colleagues are examining whether a single bout of exercise can enhance the ability of intranasal insulin to support cognitive health in aging adults with obesity by measuring brain blood flow and neuronal extracellular vesicles. Their future plans are to conduct a long-term exercise training study that assesses brain insulin sensitivity improvements in relation to cognition in older adults. 

Other Rutgers scientists on the study included Michal Beeri, director of the Herbert and Jacqueline Krieger Klein Alzheimer’s Research Center at Rutgers Robert Wood Johnson Medical School; and Daniel Battillo, a doctoral candidate in the kinesiology and applied physiology graduate program. Scientists from the National Institute of Health’s National Institute on Aging involved in the study included Dimitrios Kapogiannis, Maja Mustapic and Francheska Delgado-Peraza.